6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model

Marine Drugs

Babak Esmaeelian²  Catherine A. Abbott²  Richard K. Le Leu¹ 

[1] Flinders Centre for Innovation in Cancer, Flinders University, GPO Box 2100, Adelaide 5001, Australia; E-Mail:;School of Biological Sciences, Flinders University, GPO Box 2100, Adelaide 5001, Australia; E-Mails:

关键词: apoptosis;    azoxymethane;    bioactive natural product;    colorectal cancer;    isatin;    in vivo model;    marine mollusc;   

DOI  :  10.3390/md12010017

来源: mdpi

【 摘 要 】

Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by ¹H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC₅₀ 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.